Clinicians managing patients with chronic non-cancer pain (CNCP) are typically faced with the dilemma of providing the appropriate standard of care to alleviate suffering including the use of opioids, while not complicating recovery by exposing the vulnerable patient to the potential of opioid abuse and addiction. It has been considered the standard of care to provide patients suffering from CNCP with opioids, even on a long- term basis. However, there is ongoing debate regarding this policy of responsible opioid prescribing in chronic pain patients given the rising prevalence of prescription opioid abuse and addiction in the country (Johnston, 2008). Numerous studies have identified high prevalence rates of substance use disorder in chronic pain patients (Polantin, Kinney et al, 1993~ Compton et al, 1998~ Martell et all, 2006). Reported prevalence of opioid abuse in chronic pain patients ranges from 3-40% (Fishbain et al, 1992, 2008~ Martell et al, 2007~ Ives et al, 2006). Diagnosing abuse and addiction in patients with chronic pain on opioids is very complex. It is difficult to ascertain who will become problematic users of prescription opioids when initiating therapy. There have been attempts at mitigating this problem of predicting which patients are at risk for opioid addiction (OA), with the utilization of questionnaires and interview protocols which have been promising, but not well validated (Turk et al, 2008). This project is the first in a series of studies to assess the behavioral and genotypic characteristics of patients who develop OA. There is a growing body of evidence indicating that risk for OA has substantial genetic origins (Kreek et al, 2005). There has been considerable evidence from clinical and animal studies regarding the mu opioid receptor (MOR) gene (OPRM1) as critical to the rewarding and analgesic properties of opioid analgesics. It is the specific aim of this project to perform genome-wide analysis in approximately 2,000 patients with CNCP having been treated for OA. To date it has been difficult to identify a control group of patients who are chronically exposed to opioids but do not develop addiction. In our study, 2000 patients with chronic pain who are receiving long-term opioid therapy and who have not displayed evidence of addiction will serve as our controls. In addition, we will assess psychiatric co-morbidities, aberrant behaviors, substance use, addiction and socioeconomic factors in both groups. This will allow us to substantiate in the control group the absence of addiction and also to elucidate specific psychosocial factors and specific behaviors in the experimental group suggestive of addiction. This data will form the basis of subsequent studies in developing behavioral and genetic risk profiling for prospective testing in patients with chronic pain initiating opioid therapy.